Activation of the NLRP3 Inflammasome Is Associated with Valosin-Containing Protein Myopathy (original) (raw)

“… 37 , 38 Mcc950 not only inhibited NLRP3 inflammasome activation as evidenced by suppressing cleavage of caspase 1 and downstream interleukin IL-1 β production, but decreased apoptosis and mature IL-1 β released by HRECs. Thus, Mcc950 has an anti-inflammatory role in the pathogenesis of impaired glucose-mediated retinopathy, and these data agree with previous reports that Mcc950 can inhibit NLRP3 inflammasome activation in dermal and pulmonary inflammation, 31 crystal-induced kidney fibrosis, 33 valosin-containing protein-associated diseases, 32 cryopyrin-associated periodic syndromes, 20 , 39 , 40 hypertension, 41 and myocardial infarction. 42 …”

Section: Discussionsupporting

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Section: Discussionsupporting

“…Activation of the NLRP3 inflammasome is thought to be key for the progression of pro-inflammatory effects of retinopathy including age-related macular degeneration 18 and DR. 27 Using immunofluorescence and western blot we confirmed NLRP3 inflammasome activation in human REC of proliferative membranes, a crucial characteristic of PDR. 28 , 29 , 30 The anti-NLRP3 inflammasome effect of Mcc950 for macrophages, microglia, myoblasts and dendritic cells is well described, 31 , 32 , 33 , 34 but its effect on inflammation of HRECs is unexplored. Thus, we investigated the potency of Mcc950 for attenuating inflammation in HRECs induced by high glucose.…”

Section: Discussionmentioning

“…Recent mouse models of VCP showed that activation of the NLRP3 inflammasome is associated with VCP protein myopathy. Nalbandian et al (2017) reported a significant increase in the expression of NLRP3, Caspase 1, IL-1β, and IL-18 in the quadriceps of 12 and 24 months old VCPR155H/+heterozygous mice. Furthermore, a significant increase of IL-1β(+)F4/80(+)Ly6C(+) macrophages in the quadriceps and bones of the same mice were also observed and is positively correlated with high expression levels of TDP-43 and p62/SQSTM1 markers of VCP pathology and progressive muscle wasting (Nalbandian et al, 2017).…”

Section: Valosin Containing Protein (Vcp)mentioning

“…Over the past two decades, inflammation in PD has received great interest by many researchers, highlighting microglial activation, cytokine production and oxidative damage in the in vivo model and post-mortem [ 4 , 5 ]. Therefore, neuroinflammation represents a key role in the progressive degeneration of dopaminergic neurons and in the pathogenesis of PD [ 6 , 7 ]. This is demonstrated by the discovery of high levels of some proinflammatory cytokines, such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and many others, in the samples of the brain parenchyma and cerebrospinal fluid of affected patients from PD compared to control samples [ 8 ].…”

Section: Introductionmentioning